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The aliasing/jaggies are much more noticeable and the screen has a yellow tint you'll only notice if you compare it with the original side-by-side. You can notice upscaled text looking blurry in some games, though it's still readable.
Apart from those, I don't notice the upscaling THAT much (it could be worse, see DSi XL), I love having bigger screens, and doesn't feel so small to hold.